Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers: A case report and review of literature

Abstract

Background: Genetic factors of chronic intestinal ulcers are increasingly garnering attention. We present a case of chronic intestinal ulcers and bleeding associated with mutations of the activin A receptor type II-like 1 (ACVRL1) and phospholipase A2 group IVA (PLA2G4A) genes and review the available relevant literature.

Case summary: A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain, diarrhea, and dark stools. At the onset 6 years ago, the patient had received treatment at a local hospital for abdominal pain persisting for 7 d, under the diagnosis of diffuse peritonitis, acute gangrenous appendicitis with perforation, adhesive intestinal obstruction, and pelvic abscess. The surgical treatment included exploratory laparotomy, appendectomy, intestinal adhesiolysis, and pelvic abscess removal. The patient's condition improved and he was discharged. However, the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge. On the basis of these features and results of subsequent colonoscopy, the clinical diagnosis was established as inflammatory bowel disease (IBD). Accordingly, aminosalicylic acid, immunotherapy, and related symptomatic treatment were administered, but the symptoms of the patient did not improve significantly. Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes. ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation, respectively. This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes. Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms.

Conclusion: Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD. Orally administered Kangfuxin liquid may have therapeutic potential.

Keywords: Activin A receptor type II-like 1; Case report; Crohn’s disease; Intestinal ulcers; Phospholipase A2 group 4A; Ulcerative colitis.

Figure 1

Sanger sequencing of the activin A receptor type II-like 1 and phospholipase A2 group IVA genes in patients. Het: Heterozygote; AD: Autosomal dominance inheritance; AR: Autosomal recessive inheritance.

Figure 2

Gastroscopy results. A: Esophagus; B: Gastric fundus; C: Gastric body; D: Gastric antrum; E: Duodenal bulb; F: Descending duodenum. No obvious abnormalities are seen in the morphology and color of the esophagus. The distance between the cardia and the incisor is about 40 cm, and the dentate line is clear. The gastric fundus does not show any obvious abnormalities in the mucosa and morphology, and there is a moderate amount of mucus and yellow turbidity. The gastric body's mucosa and morphology are also normal; the gastric angle is curved and smooth. The gastric antrum's mucosa is congested and edematous, but no ulcers or masses are present. The pylorus is circular in shape and can open and close smoothly. There are no obvious abnormalities in the duodenal bulb and descending mucosa.

Figure 3

Colonoscopy results. A: Distal ileum; B: Distal ileum; C: Distal ileum; D: Surgical repair site; E: Hepatic flexure; F: Anus. The distal ileal mucosa is congested and edematous, with visible erosion and scattered patchy ulcers, covered with white fur and distributed in segments. The surrounding mucosa is accompanied by pseudopolypoid hyperplasia, presenting as cobblestone-like changes. Local mucosal protrusions, ulcers, and nodular protrusions can be seen near the hepatic flexure of the transverse colon. Suspected formation of a sinus in the anus.

Figure 4

Pathology of intestinal mucosal tissue. A: Colon (a small amount of mucosal tissue and inflammatory exudative necrosis); B: Distal ileum (ulcer formation, large numbers of inflammatory exudates and granuloma formation, and large numbers of lymphocytic plasma cell infiltration).